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J Gilchrist

Publications and source records attributed to J Gilchrist.

At least 37 records · Page 2Linked to original sources

The mahogany protein is a receptor involved in suppression of obesity.

Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor.

Amino Acid Sequence↗

A novel system for the objective classification of iris colour and its correlation with response to 1% tropicamide.

Iris colour can provide an enormous amount of information about an individual. In addition to changes with pathological conditions, the colour of the iris can be a particularly useful indicator of how well a person will respond to a topically applied ocular drug. Until recently, classification of iris colour has been subjective, ranging from a basic description ('light' and 'dark') to more detailed grading systems, such as a comparison with preset photographic standards. However, variability within observers and differences in the interpretation between observers can influence the results. Objective techniques, in this respect, possess several advantages. They are able to detect differences in colour that subjective techniques are incapable of and they provide continuous data rather than discrete categories, thus improving the accuracy of drug response predictions. This study assessed iris colour by objective means. Slit-lamp photographs of various coloured irides were taken under standardised conditions. The slides were then scanned into a computer and the colour analysed using a calibrated software package. To establish the optimum colour parameter to be used for predictions of drug response, several parameters were calculated and compared with the subject response to 1% tropicamide (maximum change in pupil size, time to maximum change and total duration of effect). Many parameters had strong correlations with drug response, but the parameters 'z', 'b' (the proportion of blue in the image) and 'y' (the proportion of yellow in the image) were found to exhibit the highest correlations. They also showed better correlations with drug response than did a current iris colour grading system.

Adult↗

Bovine IgG repertoire is dominated by a single diversified VH gene family.

Using methods based upon the PCR, we have analyzed sequences that encode the V domain of bovine Ig heavy chain. Pairwise comparison indicates that the heavy chain repertoire in cattle is dominated by a single VH gene family that is homologous to human VHII. The third complementarity-determining region (CDR3) is particularly variable and 60% of the sequences encode a CDR3 in excess of 21 amino acids. Southern blots, single-stranded conformation polymorphism analysis, and sequencing of segments from the germline indicate that the dominant VHII gene family is of small size, comprising as few as 10 unique members, and carries a very low level of diversity in CDRs 1 and 2. Comparison of germline VH sequences with those gathered from adult bovine splenic cDNA demonstrates a pattern of nucleotide substitution that is consistent with diversification through somatic hypermutation.

Animals↗

Relationship between changes in EMG and respiratory sinus arrhythmia in a study of relaxation therapy for asthma.

This paper reports the relationships among changes in cardiovagal activity, surface EMG, and measures of pulmonary function in a study of relaxation therapy for asthma. Changes in FEV1/FVC were negatively correlated with those in cardiac interbeat interval, consistent with the hypothesis that relaxation-induced changes in airway function are mediated autonomically, with increased vagal tone and/or decreased sympathetic arousal producing bronchoconstriction. Contrary to Kotses's theory of a vagal-trigeminal reflex as mediator for relaxation-induced improvement in asthma, decreases in pulmonary function occurred during relaxation sessions, accompanied by increases in cardiovagal activity, and within-session changes in frontal EMG in the first session of training were positively associated with changes in a measure of pulmonary function (FEV1/FVC). However, consistent with this hypothesis, first-session frontalis EMG changes were positively associated with changes in respiratory sinus arrhythmia, and last-session changes in cardiac interbeat interval were positively associated with changes in FEV1/FVC. The results suggest that the immediate effects of generalized relaxation instruction can be associated with a parasympathetic rebound, which, in tum, may induce countertherapeutic changes in asthma. However, the effects of specific facial muscle relaxation remain unclear.

Adult↗

ERP repetition effects in indirect and direct tasks: effects of age and interitem lag.

Event-related potentials (ERPs) were recorded for visually presented words in young and older participants while they performed two tasks. In the indirect task, participants responded to occasional target words. Some of the nontarget words were repeated after a single intervening trial, and others were repeated after a mean of 10 trials. In the direct task participants responded to every item, discriminating between words presented for the first and the second times. Compared with ERPs to unrepeated words, those to words repeated in the indirect task after either lag were more positive in both participant groups. For the short lag, this effect was larger among the older participants. In the direct task, words repeated after either lag elicited a positive shift in the ERPs of the young participants. In the older participants, short lag repeats elicited a repetition effect, but smaller than the equivalent effect among the young participants. Long lag repeats failed to elicit a repetition effect in the direct task in the older participants. The findings show that word repetition in these tasks reflects the modulation of two ERP components, which differ in their sensitivity to age-related changes in memory function.

Adult↗

A comparison of sampling efficiency and internal noise level in young and old subjects.

Contrast detection in different levels of external visual noise allows a given loss in contrast sensitivity to be attributed to either an increase in the internal noise of the visual system, a decrease in sampling efficiency, or both. Sampling efficiency indicates how effectively the available stimulus information is utilized by the visual system. The aim of this study is to investigate the effect of normal ageing on sampling efficiency and internal noise. Contrast thresholds for sine-wave gratings of 6 c/deg were measured in the presence of four (including zero) levels of externally added visual noise in young and older healthy observers. Results showed that sampling efficiencies were significantly lower for the older group compared to the younger, while the internal noise showed no significant change. The implications of the data for the relative contribution of the optical and neural systems on visual function loss with ageing are discussed. Our results suggest that the neural system plays a major role in the loss of contrast sensitivity with ageing in normal, healthy eyes.

Adolescent↗

Molecular characterization of bovine V lambda regions.

Using an inverse PCR technique with primers directed against constant region sequences, 18 V lambda regions have been isolated at random from bovine splenic cDNA for detailed analysis. On the basis of protein sequences in FR1 and their homologies to the human lambda chains NEWM and MCG, the bovine determinants can be separated into two families that have been designated V lambda 1 (94% of all clones isolated) and V lambda 2 (6% of all clones isolated). Scrutiny of the nucleotide sequences has allowed subdivision of the dominant family into V lambda 1a, V lambda 1b and V lambda 1c groupings, which represent 29, 65, and 6% of all V lambda 1 clones respectively. It appears that the size of CDR1 is V lambda group-specific--the region comprises 14 amino acids in V lambda 1a determinants and 13 residues in V lambda 1b and V lambda 1c,--whereas with a single exception, seven amino acids make up CDR2. The size of CDR3 is variable, ranging from 10 to 15 amino acids in length. Conservation of those nucleotide sequences that encode the signal peptide and FR3 has enabled us to amplify and characterize 14 V lambda 1 genes from kidney genomic DNA. Interestingly, half of the germline sequences were not represented in the data gathered from splenic cDNA, while the remaining genes could be identified as members of the V lambda 1a and V lambda 1b groups. The findings indicate that the V lambda 1 family dominates the expressed bovine light chain repertoire but that a large proportion of the germline segments from which this repertoire is derived may be nonfunctional.

Amino Acid Sequence↗

The effect of red and neutral density filters on the degree of eccentric fixation.

The reported shift of fixation to a more central position when a red filter is placed before an eye which fixates eccentrically, has never been satisfactorily explained. To further investigate this phenomenon, 14 subjects with eccentric fixation were recruited. A Wratten No. 92 filter was placed before the eccentrically fixating eye, and any change of fixation was assessed by the after-image transfer test. A neutral density (ND) filter was then used, to mimic the reduced retinal illumination caused by the red filter. The results suggest that there is a significant reduction in the eccentricity of fixation, when placing the red filter before an eccentrically fixating eye, and also when placing the ND filter. No significant difference in the effects produced by either filter was found. This suggests that it is the reduction in retinal illuminance caused by the red filter which contributes towards such improvements in fixation.

Afterimage↗

Cardiomyopathy of limb-girdle muscular dystrophy.

OBJECTIVES: This study sought to find an association between dilated cardiomyopathy and limb-girdle muscular dystrophy. BACKGROUND: Cardiomyopathy has been seen in various neuromuscular disorders, but it has not been recognized to be associated with limb-girdle muscular dystrophy. METHODS: We investigated three sisters with well documented limb-girdle dystrophy and congestive heart failure by the 3rd decade of life. All underwent noninvasive evaluation of left ventricular systolic function by both echocardiography and radionuclide scanning, and one also had cardiac catheterization. Deoxyribonucleic acid (DNA) linkage analysis was performed in these affected subjects and in the unaffected family members, and DNA was extracted from mononuclear cells with primer sequences for three chromosome 13q microsatellite markers. RESULTS: The parents had no evidence of clinical disease, but all three sisters had echocardiographic evidence of dilated cardiomyopathy. The sister with additional evidence of left ventricular dysfunction of cardiac catheterization had no coronary artery disease. The affected subjects had the same paternal allele for three potential markers of limb-girdle muscular dystrophy but different maternal alleles. The very small family size did not permit statistical confirmation or refutation of linkage for chromosome 13q markers. CONCLUSIONS: Demonstrable cardiomyopathy accompanying limb-girdle muscular dystrophy and its probable genetic associations require continued investigation by anticipating the cardiomyopathy in limb-girdle muscular dystrophy.

Adult↗

Vectors to facilitate the creation of translational fusions to the maltose-binding protein of Escherichia coli.

A set of vectors has been constructed to facilitate the fusion of heterologous sequences to the C terminus of the maltose-binding protein (MBP) of Escherichia coli. The plasmids carry a cloning region comprising two blunt cloning sites, a BamHI site and multiple stop codons, and this has been placed in each reading frame so that translational fusions to MBP can be generated and manipulated with ease. To demonstrate the utility of this system, recombinant proteins have been engineered in which staphylococcal enterotoxin A has been fused to MBP.

ATP-Binding Cassette Transporters↗

Relaxation and music therapies for asthma among patients prestabilized on asthma medication.

One hundred six asthmatic subjects were medically prestabilized, then assigned to eight sessions of progressive relaxation, music, or a waiting-list. Seventy-two subjects completed treatment, of which 37 were evaluated in the laboratory with measures of forced expiratory flow. Relaxation-group subjects reported feeling the most deeply relaxed and produced the greatest improvement in forced expiratory flow during the last presession assessment period. All groups evidenced decreases in asthma symptoms. All groups showed decreases in pulmonary function immediately after relaxation sessions. None of the changes in pulmonary function reached levels that are accepted in drug trials to be of clinical significance, and the therapeutic changes occurred only in the situation where training was rendered. Listening to music produced greater decreases in peaks of tension than progressive relaxation, and it produced greater compliance with relaxation practice, but it did not produce any specific therapeutic effects on asthma.

Adolescent↗

The value of HMPAO SPECT scanning in the diagnosis of early Alzheimer's disease in patients attending a memory clinic.

The value of hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) as a diagnostic test for Alzheimer's disease (AD) was assessed in 44 patients attending a Memory Clinic. A comprehensive physical and psychiatric examination and detailed neuropsychological tests were used to arrive at a clinical diagnosis, in accordance with NINCDS-ADRDA criteria. The mean patient age was 69 (range 59-84) years, and the mean score on the Mini-Mental State Examination (MMSE) was 24 (range 7-30). Of 26 patients with a clinical diagnosis of AD, only 15 demonstrated a scan pattern strongly suggestive of AD. Four scans were normal, four showed evidence of ischaemic change and three were in the category 'other', one of which showed bilateral frontal hypoperfusion, but normal temporoparietal flow. Of the eight patients considered by clinical criteria to be non-demented, no scan showed an AD pattern, but three showed an ischaemic pattern. Both of the patients diagnosed clinically as suffering from multi-infarct dementia showed SPECT scan evidence of ischaemic change. Of the remaining eight patients with other clinical diagnoses only one scan suggested AD. We conclude that the HMPAO SPECT scan appearances which arise from AD in the early stages of the disease do not on their own allow the disease to be accurately diagnosed, but they may be useful if interpreted in conjunction with other imaging techniques.

Aged↗

Needlestick injuries: the shock and reality.

It has been a typically busy Saturday night in the emergency department. Then, near midnight, a trauma casualty was admitted and an incident occurred that would occupy Suzanne Smith's thoughts for months to come. When starting an intravenous line on this patient, Suzanne spiked herself with a needle. Later the patient was taken to the intensive care unit and placed on a ventilator. Suzanne was overcome with fear that she might have contracted AIDS. Her fears intensified when she learned that the patient, Mr. Norman, was a heroin addict.

Fear↗

Contrast detection in noise: a new method for assessing the visual function in cataract.

The detectability of a signal decreases in the presence of externally added visual noise. A linear relation exists between the energy of a signal at threshold and the spectral density of the added visual noise. This relation, represented by contrast detection in noise function, allows a given loss in contrast sensitivity (CS) to be attributed to an increase in the internal intrinsic noise and/or a decrease in the detection efficiency of the observer. Intrinsic noise gives a measure of the random background noise within the visual system, whereas detection efficiency is a measure of how effectively the observer utilizes the available stimulus information. Recent work shows that neural dysfunction produces a decrease in the detection efficiency, whereas optical deficits produce a change in the intrinsic noise only. We investigated whether the CS loss in cataract can be attributed to either a change in intrinsic noise, in detection efficiency, or both. Contrast detection in noise functions was measured for 10 uniocular cataract patients. Comparison between the two eyes showed no significant difference in detection efficiency, although the intrinsic noise increased significantly in the cataractous eye. The data suggest that detection efficiency may provide a measure of neural visual function behind a cataract and, conversely, that intrinsic noise provides a measure of the visual effect of the cataract itself. We discuss the implications of intrinsic noise as a measure of cataract for both clinical assessment and research.

Aged↗